How does psilocybin affect the body? A research-informed guide for curious seekers

Jan 19

Research into psilocybin is growing, and there are now laws allowing people to use it in therapeutic modalities in states like Oregon. Psilocybin and its active metabolite psilocin are considered controlled substances, and public interest in their therapeutic potential is increasing despite their legal status.

Psilocybin is one of the most studied psychedelics, with many clinical studies exploring its use for treating depression, anxiety, substance use disorders, and end-of-life anxiety. However, more research is needed to fully understand its effects and to establish safe and effective treatment protocols.

Psilocybin is classified as a Schedule I substance in the United States, meaning it has a high potential for abuse and no accepted medical use. In Canada, the production, sale, and possession of magic mushrooms containing psilocybin are illegal under the Controlled Drugs and Substances Act (CDSA).

Internationally, psilocybin and psilocin are controlled under the United Nations Drug Control Conventions. There are currently no approved therapeutic products containing psilocybin in Canada or elsewhere. However, Health Canada allows access to psilocybin through clinical trials and the Special Access Program for patients with serious conditions, with exemptions granted based on regulatory compliance and public interest considerations.

To understand how psilocybin affects individuals, we need to know how the compound works in the body and brain. Understanding how psilocybin acts neurologically, physiologically, and emotionally helps set realistic expectations of the experience. In this guide, we discuss the way that psilocybin is metabolized and its impact on serotonin receptors and brain networks.

While this substance is generally safe, individuals will have a different experience depending on their intentions, the environment in which they are using psilocybin, and their psychological readiness; therefore, it is important that people using this psychedelic are in a supportive, therapeutically regulated environment to minimize risk and maximize the benefit of their psilocybin experience.

Key takeaways

Psilocybin is biologically inactive until converted into psilocin, which acts on serotonin receptors — especially 5-HT2A — throughout the brain.
Psilocin disrupts normal network patterns such as the default mode network (DMN), increasing connectivity and flexibility in brain signaling.
Typical physical effects include mild increases in heart rate and blood pressure, pupil dilation, temperature changes, and occasional nausea.
Psilocybin can create profound shifts in perception, emotion, and meaning through its effects on cortical and limbic systems.
Research shows psilocybin promotes neuroplasticity, with changes in brain pathways that may last weeks to months.
Risks increase for individuals with cardiac disease or personal/family history of psychosis or bipolar disorder, emphasizing the need for screening and safe, supervised settings.

You might like to read: What is psilocybin? Understanding magic mushrooms and their effects

What happens in the body when you take magic mushrooms?

When psilocybin is ingested, it is absorbed through the digestive tract and undergoes a metabolic transformation. It is converted into psilocin, the active metabolite that enters the bloodstream and crosses the blood-brain barrier. Depending on an individual's metabolism, the dosage, and whether the compound is consumed as dried mushrooms or a standardized formulation, effects typically begin within 20 to 60 minutes.

Once psilocin enters the body, it binds to serotonin receptors located in various parts of your nervous system. It initiates several body-related and psychological changes. However, people's experiences with psilocin can differ greatly from one user to another, and are not strictly related to how the drug works chemically.

Individual factors — such as genes, current mental state, immediate surroundings/environment (set - "place" as well), and current state of readiness/emotional state — greatly affect how a given individual interprets the biological alterations caused by psilocin.

Psilocybin pharmacology: How the compound interacts with the body

Psilocybin is technically a "prodrug," meaning it is biologically inactive until it is metabolized. Liver enzymes and gut metabolism rapidly convert it into psilocin, which is responsible for nearly all psychoactive effects. Modern PET imaging studies have shown a strong correlation between peak psilocin concentrations in the blood and the perceived intensity of the psychedelic experience.

The primary mechanism of action involves psilocin binding to serotonin receptors, most notably the 5-HT2A receptors located in the cortical and limbic regions. These areas are responsible for perception, emotional processing, and high-level cognition. By binding here, psilocin disrupts and disinhibits standard network signaling.

This is why the experience is often described not as a simple hallucination, but as a fundamental shift in how the brain processes information. At therapeutic doses, receptor occupancy can reach approximately 70 percent.

Beyond serotonin, psilocybin triggers downstream signaling involving glutamate, mTOR, and BDNF (Brain-Derived Neurotrophic Factor). These pathways are associated with neural rewiring and emotional processing. Animal studies have even indicated an increased expression of neuroplasticity markers within just 90 minutes of dosing, suggesting that the "re-wiring" process begins almost immediately.

You can also read: Psilocin vs psilocybin: key differences and their effects explained

How psilocybin affects brain networks

One of the most significant neurological shifts occurs within large-scale brain networks. The Default Mode Network (DMN), which is associated with self-referential thought and the "ego," becomes less synchronized, or desynchronized. This allows other brain networks that do not usually communicate to increase their cross-talk.

Recent 2024 MEG and fMRI studies demonstrate this increased functional connectivity and "entropy," leading to an altered sense of self and the ability to form novel associations.

Visually altered experiences (e.g., changes in color, time, and space) are common among participants due to these network changes (sometimes perceived as sensory hallucinations).

Importantly, though these experiences can be dramatic, they occur only temporarily due to disinhibition of the cortex—not because of structural changes within the brain. Furthermore, psilocybin has the potential to amplify emotional experiences and cause the user to view their environment in a new light, which can be both empowering and challenging.

Increased amygdala activity is also associated with psilocybin use. These experiences can lead to healthy emotional expression and, at times, to mystical or transcendent experiences characterized by feelings of connectedness and understanding. In clinical settings, many of these experiences have been reported as major contributors to successful therapy outcomes.

If you’re curious about the therapeutic use of psilocybin, you can see more details about our retreats here.

How psilocybin affects the body

Physiologically, psilocybin primarily affects the autonomic nervous system. It produces mild to moderate increases in heart rate and blood pressure, peaking within the first hour. While tachycardia is reported in about 7 percent of clinical cases, clinically meaningful arrhythmias are extremely rare in healthy, screened adults. However, this elevation does mean that those with structural heart disease or uncontrolled hypertension must exercise caution.

Other common autonomic responses include pupil dilation (mydriasis), mild tremors, temperature fluctuations, and nausea. The nausea is often brief and can be exacerbated by the chitin in whole dried mushrooms; standardized extracts used in clinical or regulated settings typically cause less gastrointestinal distress. These symptoms are generally self-limiting and resolve as the compound is metabolized.

However, some psilocybin users risk accidental poisoning from eating a poisonous mushroom by mistake, which can lead to serious health risks. While most adverse side effects of psilocybin are mild or moderate and may resolve with time, some people may require medical treatment for severe reactions or poisoning. Prompt medical intervention is crucial in cases of suspected mushroom poisoning or severe symptoms.

Neuroplasticity: What happens after the acute experience?

The effects of psilocybin extend far beyond the 6-to-8-hour experience. Both human and animal studies show that psilocybin "loosens" rigid brain patterns associated with rumination and depression. Research indicates an increase in dendritic spine density in prefrontal regions that can last for weeks, facilitating what scientists call a "window of plasticity."

This period of enhanced cognitive flexibility is why integration work is so vital. By shifting connectivity patterns long-term, psilocybin helps individuals move away from entrenched habits of thought. This sustained change in network organization supports the potential for lasting therapeutic transformation when the experience is paired with professional guidance.

Risks, contraindications, and safety considerations

While psilocybin has the potential to provide significant benefits, it should not be viewed as a treatment option for everyone.

The cardiovascular system can be temporarily placed under stress by the use of psilocybin; therefore, which means individuals with existing heart disease or other cardiovascular conditions must be medically screened before considering treatment with this substance.

Additionally, individuals with a history (either personally or within their immediate family) of psychotic disorders (schizophrenia, schizoaffective disorder, and delusional disorder) or bipolar disorder are at greater risk for experiencing a return of mania/psychosis. Environmental factors can also significantly affect the safety of psilocybin-assisted therapy. The risk of panic or "bad trip" is greatly increased in cases of unsupervised use.

In a legal, regulated context, psychological preparation and the presence of trained facilitators mitigate these risks, ensuring the participant remains safe even during challenging emotional peaks.

You might be interested in: Questions to ask before booking a psilocybin retreat

Essential profiles of psilocybin interaction

Neurological impact: Psilocybin acts primarily as a 5-HT2A partial agonist, driving shifts in perception. By desynchronizing the Default Mode Network and increasing global connectivity, it fosters the cognitive flexibility necessary for psychological insight.
Physiological response: Expect mild cardiovascular stimulation (increased heart rate and blood pressure) alongside autonomic effects like pupil dilation and temperature shifts. These are typically low-risk in medically screened participants.
Healing potential: Rapid synaptic changes and neuroplasticity markers suggest that psilocybin may physically "prime" the brain for recovery from mood disorders and addiction.
Primary safety barriers: The most significant contraindications involve structural heart disease, uncontrolled hypertension, and a personal or family history of psychotic or bipolar disorders.

Understanding psilocybin helps prepare for a safe, supportive journey

Psilocybin affects the body through predictable neurological and physiological pathways. While the compound has a strong safety profile for healthy adults, the experience unfolds within a complex emotional context. Learning how it interacts with your biology empowers you to make informed decisions and approach the experience with clarity and respect.

For those curious about how psilocybin might support personal exploration or emotional growth, Oregon’s legal framework offers a path forward. At Confluence Retreats, we provide both group and private programs centered on preparation, facilitation, and integration within a safe, grounded environment.

For more information and to tailor a program that meets your needs schedule a free Exploration Call and don’t forget to follow us on Instagram. We are committed to providing a safe, nurturing, and transformative experience.